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Th cells are the major effector cells in transplant rejection and can be divided into Th1, Th2, Th17, and Treg subsets. Th differentiation is controlled by transcription factor expression, which is driven by positive and negative cytokine and chemokine stimuli at the time of T cell activation. Here we discovered that chemokine platelet factor 4 (PF4) is a negative regulator of Th17 differentiation. PF4-deficient and platelet-deficient mice had exaggerated immune responses to cardiac transplantation, including increased numbers of infiltrating Th17 cells and increased plasma IL-17. Although PF4 has been described as a platelet-specific molecule, we found that activated T cells also express PF4. Furthermore, bone marrow transplantation experiments revealed that T cell-derived PF4 contributes to a restriction in Th17 differentiation. Taken together, the results of this study demonstrate that PF4 is a key regulator of Th cell development that is necessary to limit Th17 differentiation. These data likely will impact our understanding of platelet-dependent regulation of T cell development, which is important in many diseases, in addition to transplantation., Introduction Platelets are the cellular mediator of thrombosis, but it is becoming increasingly evident that platelets actively participate in inflammation and immune responses (1-5). Platelets either initiate or accelerate the [...]

BACKGROUND. It is known that extremely premature infants do less well than more mature infants, and this fact has led some countries to adopt a "cutoff for viability" using birth weight or gestation. Infants affected by intrauterine growth retardation are at additional risk of poor outcome. There are few data to inform decisions about viability and (dis)continuation of intensive care when both extreme pre-maturity and severe growth retardation are present. OBJECTIVE. We focused on (1) premature infants affected by marked intrauterine growth retardation to determine if there was a cutoff weight centile below which the mortality sharply increased and (2) the short-term outcome of extremely premature and growth-retarded infants to determine a cutoff for viability. METHODS. We evaluated preterm infants of 22-32 weeks' gestation if they were alive at the onset of labor and born to European mothers resident in the Trent (United Kingdom) health region between 1994 and 2003. Infants were categorized into 6 weight centiles, and infants in each category were assessed for survival to discharge from the neonatal unit, duration of respiratory support, length of stay in the neonatal unit, and the age at death in nonsurvivors. RESULTS. We identified a total of 8228 infants who met the study criteria. Of these, 4448 infants were male, 6194 were from singleton pregnancies, and 2887 were born at [less than or equal to] 28 completed weeks of gestation. Survival to discharge was markedly reduced in the infants born at [less than or equal to] 28 weeks of gestation with a birth weight less than the 2nd centile. Stillbirth was inversely related to birth weight centile in infants born before 29 weeks of gestation. CONCLUSIONS. The survival for infants born at [less than or equal to]28 weeks' gestation and having a birth weight in less than the 2nd centile is poor, and consideration should be given to modifying their management. Key Words birth weight, extreme preterm, intrauterine growth restriction, outcome, mortality, "HOW MUCH DOES he/she weigh?" is often the next question parents ask after identifying the gender of their new infant. This probably reflects a widely held lay public view that [...]

Objective. To determine the risk of chronic lung disease (CLD) in small for gestational age (SGA) preterm infants in comparison to appropriately grown and large for gestational age (LGA) infants. Methods. Observational study derived from a geographically defined population (Trent Health Region, United Kingdom). All preterm infants of [less than or equal to] 32 completed weeks' gestation born to Trent resident mothers admitted to neonatal units between 1995 and 1999 (inclusive) were included. Birth weight percentiles were created for the whole population, and infants were classified as SGA infants (if Results. Four thousand fifty-one preterm infants [less than or equal to] 32 weeks' gestation were identified. SGA infants showed higher mortality before 28 days' postnatal age and 36 weeks' PMA as compared with reference group infants (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.49-2.72; and OR: 2.00, 95% CI: 1.49-2.69), respectively. SGA infants showed a significantly greater risk of developing CLD, both at 28 days' and 36 weeks' PMA as compared with the reference group infants (OR: 1.34, 95% CI: 1.03-1.74; and OR: 1.87, 95% CI: 1.39-2.51), respectively. LGA infants showed a trend toward a reduced incidence of CLD in comparison to the reference group, which was statistically significant for the 36 weeks' definition (OR: 0.76-28 weeks, 95% CI: 0.57-1.01; and OR: 0.55-36 weeks, 95% CI: 0.37-0.81). Conclusions. Fetal growth seems to influence mortality in general and morbidity, attributable to CLD, in particular in preterm infants. SGA preterm infants are at higher risk of death before 28 days' and 36 weeks' PMA and CLD by both definitions. LGA infants show reduced risk of CLD. Pediatrics 2003;111:483-487; prematurity; chronic lung disease, intrauterine growth retardation, small for gestational age, bronchopulmonary dysplasia., ABBREVIATIONS. CLD, chronic lung disease; PMA, postmenstrual age; VLBW, very low birth weight; SGA, small for gestational age; LGA, large for gestational age; OR, odds ratio; CI, confidence interval. Chronic [...]